Oxadiazoles structure-activity relationship

Ab initio calculations, correlations of molecules geometries, spectroscopic data with chemical properties, and quanta-tive structure-activity relationship have been conducted for both furazans and furoxans. Thus, the structures of 1,2,5-oxadiazole (furazan) and benzo[c][l,2,5]oxadiazole (benzofurazan) have been calculated by ab initio and Becke3-LYP... 

C-H and N-H bond dissociation energies (BDEs) of various five- and six-membered ring aromatic compounds (including 1,2,5-oxadiazole) were calculated using composite ab initio CBS-Q, G3, and G3B3 methods. It was found that all these composite ab initio methods provided very similar BDEs, despite the fact that different geometries and different procedures in the extrapolation to complete incorporation of electron correlation and complete basis set limit were used. A good quantitive structure-activity relationship (QSAR) model for the C-H BDEs of aromatic compounds... 

Khan MTH, Choudhary MI et al (2005) Structure-activity relationships of tyrosinase inhibitory combinatorial library of 2,5-disubstituted-l,3,4-oxadiazole analogues. Bioorg Med Chem 13 3385-3395... 

Furazan 1,2,5-oxadiazole) derivatives Combretafurazan, Fig. (11)), have been recently synthesized via a Mitsunobu reaction of vicinal dioximes [33]. Combretafurazans are more potent in vitro cytotoxic compounds compared to combretastatins in neuroblastoma cells, yet maintaining similar structure-activity relationship and pharmacodynamic profiles. 

Figure 19.7 Structure-activity relationship (SAR) of l,2,4-oxadiazol-CH2-A-allyl derivatives in the Ames test.

Muster W, Albertini S, Gocke E. Structure-activity relationship of oxadiazoles and allylic structures in the Ames test An industry screening approach. Mutagenesis 2003 18(4) 321-9. 

Sauerberg, R, Kindtler, J. W., Nielsen, L., Sheardown, M. J., Honord, T. Muscarinic cholinergic agonists and antagonists of the 3-(3-alkyl-l,2,4-oxadiazol-5-yl)l,2,5,6-tetrahydropyridine type synthesis and structure-activity relationships. J. Med. Chem. 1991, 34, 687-692. 

Table 2 shows the structure-activity relationships of the compound library of the 2,5-disubstituted 1,3,4-oxadiazoles 25-43 against the enzyme... 

Cerecetto H, Maio RD, Gonzalez M, Risso M, Saenz P, Seoane G, Denicola A, Peluffo G, Quijano C, Olea-Azar C (1999) 1,2,5-Oxadiazole N-oxide derivatives and related compounds as potential antitrypanosomal dmgs structure-activity relationships. J Med Chem 42 (11) 1941-1950. doi 10.1021/jm9805790... 

Diary] and triaryl or naphthyl carbamates exhibit low herbicidal activity. The substitution of the aryl radical for a heterocyclic radical gives heterocyclic alkyl and dialkyl ureas, of which many examples have been prepared in recent years. The herbicidal activity of urea derivatives containing a heterocyclic radical, such as benzthiazole, thiazole, thiadiazole, oxadiazole and pyridine, is favourable if one or two methyl groups are substituted at the N -nitrogen. The carrier of total or selective action in these derivatives is presumably the heterocyclic part of the molecule. More recently several new groups of compounds have become known, mainly in the patent literature, for which the structure-activity on relationships are still to be elucidated. 

---